We have devised a genetic selection system such that bacteria which have a defect in one of the enzymes which modifies nucleotides in tRNA will fail to permit growth of certain viruses at restrictive temperature. These viruses are strains which contain genetic information for suppressor tRNA and also contain mutations which must be suppressed by this tRNA for virus growth. Thus the system enables us to learn the functional role of many modified bases in tRNA. In the past year we have proven the feasibility of this system. We now are engaged in applying it to a larger collection of viruses containing various suppressor tRNAs. It is our intention to establish a sizable (10-100) collection of mutant E. coli and then to document what function of tRNA mediated metabolism requires the particular modified base which was defective in the mutant. By this method we will better understand an area of genetic disease which now is totally uncharted. The metabolism of tRNA may well lead to new understanding of the needs for minerals, cofactors and vitamins. This work also provides the necessary basis for future workers to explore these areas in higher organisms including man.